OBJECTIVES: 1. Clinical: We need better methods to identify hypertensive patients who respond unfavorably to drugs and who can be cured by specific adrenal surgery. Currently, measurements of plasma renin activity are widely used to categorize hypertensive disorders, but do not take into account the possible presence of a qualitatively different form of renin ("big renin"), whose sources, activity, and significance are quite different from those of normal renin. These clinical and methodologic problems are addressed by the proposed studies of hypertensive patients before and after treatment with a single drug or procedure, whose effect on blood pressure will be correlated with hemodynamic, renal, and endocrine functions. New agents affecting renin activity will be tested as they are released for investigational use. 2. Normal and abnormal physiology: These are considerable gaps in our knowledge concerning the regulation of aldosterone secretion in normal man and the alterations which occur in hypertensive patients. Recent developments in the protein binding and metabolic clearance of aldosterone can significantly affect our interpretation of plasma aldosterone data in normal and hypertensive people. We propose to study aldosterone binding to plasma proteins, in relation to concentrations of cortisol and transcortin, to evaluate the metabolic clearance (MCR) and concentration of free (unbound) aldosterone in plasma of hypertensive patients. Control studies in normal people, recently completed, show remarkable changes in protein binding and MCR of aldosterone as plasma cortisol concentration is increased. The effects of increased transcortin concentration, induced by estrogen or oral contraceptives, on aldosterone distribution and metabolism will be studied by in vitro tests including dialysis and gel filtration. MCR and adrenal secretory activity will be observed during proposed procedures in patients, which will aid in improving understanding of the control of adrenal secretion. Computer simulation is used to test theoretical basis for observed results.